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Hookworm disease is one of the tropical neglected diseases that significantly impacts human health to varying degrees. Hookworms produce various proteins to facilitate host invasion and immune evasion. Despite available treatments, reinfection is common, underscoring the need for effective vaccines. However, the complexity of the hookworm's life cycle poses a challenge in understanding the immune response in the vaccine candidates. Reverse vaccinology (RV) offers a powerful approach to understand the immune response by using various bioinformatics tools. This study begins by identifying hookworm antigens capable of inducing host immune responses, followed by docking analysis with different dendritic cell (DC) receptors to investigate the immunological response of antigenic peptides and further correlated to the immunogenicity findings in clinical trial. Necator americanus GlutathioneS-Transferase-1 (Na-GST-1), a known immunogenic protein from Necator americanus, was selected for docking due to its strong antigenic properties. Fifteen DC receptors were evaluated against Na-GST-1, of which seven receptors (TLR2, TLR3, TLR4, TLR7, DEC-205, CD206, and CD36) exhibited stronger predicted interactions, as indicated by stronger binding affinities with Na-GST-1 utilizing various immunoinformatic tools. These receptors are associated with the mediation of Th1/Th2 immune responses, suggesting a potential correlation between docking affinity and the predicted immunogenicity of Na-GST-1. Overall, this study provides valuable insights into DC receptor-antigen interactions and demonstrate a computational approach for assessing the potential of hookworm antigens to engage DC receptors, thereby supporting rational hookworm vaccine design. These findings support the application of early in silico strategies for advancing vaccine candidates against hookworm infection and strengthening control efforts for neglected tropical diseases.
Cryptocaryon irritans Brown, 1951, a ciliated protozoan, is the pathogen of cryptocaryoniasis (white spot disease) in marine fish, causing substantial morbidity and mortality, particularly in tropical and subtropical regions. This is the first study to investigate the antiparasitic activity of baohuoside I, a natural flavonoid isolated from Epimedium brevicornu Maxim., against C. irritans. In vitro exposure to baohuoside I suppressed theront viability and tomont hatching in a dose- and time-dependent manner, inducing an apoptosis-like death in both stages, characterized by ciliary detachment, mitochondrial disruption, nuclear condensation, and extensive vacuolization, as evidenced by transmission electron microscopy and Annexin V-FITC/PI staining. Further studies demonstrated that baohuoside I elevated the intracellular Ca2+ and reactive oxygen species levels in tomonts, indicating Ca2+ overload and oxidative stress. Transcriptomic analysis of infected Larimichthys crocea skin revealed that baohuoside I upregulated immune-related genes while downregulating pro-inflammatory genes, concurrently enhancing host serum acid phosphatase activity and mitigating oxidative stress in enzyme activity assays. In vivo trials showed that oral administration of baohuoside I reduced trophont attachment and improved fish survival. It did not exhibit hemolytic activity at concentrations effective against the parasites. Collectively, these findings elucidate a multi-target mechanism of baohuoside I, highlighting its potential as an eco-friendly therapeutic agent for cryptocaryoniasis control in marine aquaculture.
This study reports the first confirmation of Caribbean ciguatoxins (C-CTXs) in fish samples from the South Atlantic region, specifically the Fernando de Noronha archipelago (Brazil). The work was based on fish samples opportunistically collected by local health authorities in connection with suspected ciguatera poisoning cases and from related commercial settings, rather than on a prospective field survey. Samples were analyzed using methodologies developed and validated during the two phases of the EuroCigua project, and EuroCigua reference materials were used to support toxin characterization. C-CTXs were confirmed in fish species commonly associated with ciguatera poisoning, particularly Seriola dumerili and Sphyraena sp., with toxin profiles resembling those previously reported in Caribbean and East Atlantic areas. These findings provide the first analytical evidence of C-CTX occurrence in Brazil and support the need for strengthened surveillance and future targeted investigations in tropical and subtropical areas where ciguatera risk remains insufficiently characterized.
Aedes aegypti and Aedes albopictus mosquitoes are the primary vectors of tropical diseases, including dengue fever (DHF), chikungunya, and Zika, particularly in tropical regions such as Malaysia. Vector control efforts are now increasingly focused on biological and environmentally friendly approaches, one of which is using insect growth regulator (IGR)-based insecticides such as pyriproxyfen. Pyriproxyfen works by disrupting the metamorphosis process of mosquito larvae into adults without causing direct death, but it is effective in inhibiting the emergence of adult mosquitoes by more than 90%, depending on the dose and environmental conditions. This study evaluated the concentration-dependent effects of pyriproxyfen on laboratory and field populations of Aedes spp. Laboratory strains exhibited 100% adult mortality at 1.04 ppm (Ae. aegypti) and 1.08 ppm (Ae. albopictus), whereas field populations required 1.15 - 1.71 ppm depending on locality. LC50 values were lowest in laboratory strains (0.267 ppm for Ae. aegypti and 0.236 ppm for Ae. albopictus), while field strains ranged from 0.326 to 0.571 ppm. LC95 values followed a similar trend, with 1.026 ppm (Ae. aegypti) and 1.107 ppm (Ae. albopictus) in laboratory strains. Inhibition of emergence (IE%) was high in laboratory strains, reaching 97.89% at 0.50 ppm in Ae. aegypti and 63.54% at 0.50 ppm in Ae. albopictus. Field populations required higher concentrations for similar suppression, with IE% ranging from 17.68 - 98.23% in Ae. aegypti and 13.14- 98.24% in Ae. albopictus, peaking at 1.50 ppm. From this finding, it is suggested that pyriproxyfen effectively inhibits adult emergence in both laboratory and field populations, with laboratory strains more sensitive at lower concentrations and field strains responding at higher doses. These results provide strong evidence for pyriproxyfen as an effective, adaptive, and sustainable component of integrated vector management in Malaysia.
The Nobel Turing Challenge (NTC) proposes AI systems capable of autonomous, Nobel-level scientific discovery. The IJNTC2025 workshop convened researchers from India and Japan to advance this goal in health and biomedicine. This perspective synthesizes four themes: knowledge extraction, laboratory automation, hypothesis generation, and equitable healthcare applications. It identifies how Japan's robotics and precision AI expertise and India's large-scale data infrastructure and frugal innovation offer complementary strengths for collaborative progress toward the NTC.
Leishmaniasis, caused by Leishmania spp., is one of the most neglected tropical diseases and poses a serious threat to public health, accounting for at least one million new cases each year. There is no available human vaccine. In this study, we explored the potential of Leishmania extracellular vesicles (EVs) as a vaccine platform, employing a production and purification method to aid clinical translation and facilitate vaccine development in an affordable setting. Immunization with Leishmania major and Leishmania infantum EVs elicited robust humoral and cellular immune responses, providing protection and cross-protection against live parasite challenge in selected susceptible BALB/c mouse infection models. Inclusion of specific adjuvants significantly influenced vaccination outcome, highlighting the importance of adjuvant choice in determining effective protection versus susceptibility. Our findings demonstrate the potential of EVs not only for the prevention of leishmaniasis but also for broader applications in combating other protozoan infections.
In cancer diagnosis and treatment, 'accurate diagnosis' and 'targeted therapy' are the primary focus and key goals of many research groups. Metal-organic frameworks (MOFs) have attracted considerable attention in cancer diagnosis and treatment owing to their structural diversity and multifunctionality. Starting in 2010, MOFs with targeting capabilities have been gradually developed and applied in the field of biomedicine. This Review provides readers with a simple guide to help design bioenabled MOFs for specific bioapplications. First, construction strategies of MOFs with targeting functions are classified, including non-covalent interaction, covalent interaction and coordinative interaction strategies. Then, the applications of MOFs modified by antibodies, peptides, aptamers, carbohydrates, cell membranes and other targeting strategies are discussed. Finally, the future challenges and prospects for constructing MOFs with targeting functionalities are outlined to provide guidelines for the next generation of MOFs capable of achieving accurate cancer diagnosis and treatment and to accelerate the development of MOFs in clinical applications.
Lymphatic filariasis (LF) remains a significant public health challenge in many tropical regions where the disease is endemic. In Malaysia, LF is found in small pockets across the country. Asymptomatic carriers play a critical role in transmission but are often undetected. This report details an investigation of an asymptomatic filariasis reported by local health authorities involving an 83-year-old female patient residing in the Bako area, Sarawak. Despite being immobile due to a stroke, routine screening identified an infection with Brugia malayi through microscopy and a rapid diagnostic test. Interestingly, the patient exhibited no acute or chronic symptoms typically associated with filariasis. Contact tracing among her family members revealed that her son was also infected. Both patients received treatment with diethylcarbamazine (DEC) at a dosage of 6 mg/kg, along with albendazole 400 mg and ivermectin 12 mg. Preventive measures included health education, entomological studies, and the implementation of a 'Test & Treat Filariasis' program in the village. By documenting both the index case and a secondary asymptomatic case within the same household, the study provides a strong example of how routine screening and contact tracing can identify hidden sources of infection. This adds significant value to LF elimination strategies and emphasizes the importance of community-level surveillance programs. Coordinated efforts by health authorities, including contact tracing, environmental assessments, and targeted treatment, are essential for controlling the spread of LF and safeguarding public health.
Lanthanide-based metal-organic frameworks (Ln-MOFs) have been well developed in recent years because of their unique optical properties, including long luminescence lifetimes, sharp emission peaks, large Stokes shifts, and tunable luminescence colors, which enable them to be used for high-performance luminescence-based detection. In order to gain a comprehensive understanding of luminescence sensing, this paper reviews how Ln-MOFs offer highly sensitive and selective detection in areas such as environmental monitoring, biomedicine, food safety, and public security. In addition, this paper addresses the luminescence sensing processes and recent advances in Ln-MOFs. It also discusses the design strategies and provides a forward-looking view on potential prospects and challenges.
Both short and long sleep duration have been associated with poor glycemic control and an increased risk of developing type 2 diabetes mellitus. Although sleep duration may differentially modify the effects of genetic risk factors for type 2 diabetes, this has not been systematically investigated. In the present study, we conducted genome-wide gene by sleep duration meta-analyses, separately assessing interactions of short and long sleep, for fasting glucose, fasting insulin, and hemoglobin A1c in up to 489,309 individuals without diabetes from seven different population groups. In total, 16 loci were identified to interact with sleep duration - six with short sleep and ten with long sleep. Of these, four loci were identified through cross-population meta-analysis. Mapped genes exhibit pathway connections to pericyte apoptosis, NMDA receptor activity, the GLUT1 receptor, neurological health, and sleep architecture. Eleven loci (VRK2, PCDH7, TFAP2A, CAP2, PAPPA, ZCCHC2, MYH9, SGIP1, JAKMIP3, RRAS2, MAPT) have not been reported in previous glycemic trait genome-wide association studies. Interaction loci identify divergent biological mechanisms for short and long sleep duration influencing glycemic control, suggesting specific pathways of intervention for precision medicine approaches to diabetes prevention and management.
Whole-genome sequencing of bacterial pathogens can positively impact infectious disease management in clinical contexts, both in individual settings and by assisting infection prevention efforts. However, logistical issues have often prevented its translation into clinical settings. Oxford Nanopore Technologies (ONT) platforms are flexible and affordable and now offer accuracy comparable to other sequencing platforms, making them uniquely well-suited for clinical bacterial isolate sequencing. We sought to determine the best methods for implementing ONT sequencing into clinical settings by benchmarking multi-locus sequence typing (MLST), core genome multi-locus sequence typing (cgMLST), antimicrobial resistance (AMR) and core genome SNP (cgSNP) typing against the genomic automated gold standard. We sequenced 199 Enterobacterales isolates with Illumina and ONT platforms and assessed performance based on sequencing chemistry, basecaller, basecalling model, assembly status, assembly polishing and sequencing depth. Modern ONT data generated perfect MLST and AMR allelic variant calls and correctly classified a median of 99.5% of cgMLST loci. Illumina and kmer-based SNP typing failed to call 9-28 SNPs per 1,000 sites due to poor sensitivity in repetitive regions of the reference genome, while ONT's long reads generated perfect SNP calls across the entire genome using simulated readsets. Using real sequencing data to identify putative transmission pairs, ONT read-based methods were concordant with traditional Illumina approaches in 155-158/158 (98.1-100%) of isolate pairs. We also provide specific recommendations on sequencing depth and basecalling model based on the time and computational resources available to the user. This study demonstrates the viability of modern ONT data for highly accurate characterization of bacterial pathogens to support their future integration into clinical settings.
Entamoeba histolytica (E. histolytica) is a protozoan parasite that causes amoebiasis in humans. It is prevalent in developing countries, particularly in areas with inadequate sanitation and limited access to clean water. While some data on the infection in the Malaysian population is available, comprehensive data on the overall prevalence is lacking. Our study aimed to determine the prevalence of E. histolytica in Malaysia through systematic review and meta-analysis using data published up to 2025. Fourteen studies covering diverse population groups from various states in Malaysia, including rural and urban residents, schoolchildren, indigenous communities, and high-risk populations were reviewed. We found an overall pooled prevalence of 7% with high heterogeneity (I² = 92.5%). Prevalence varied widely by state and population subgroup, with higher rates in Pahang (18%) and among aboriginal schoolchildren (16%). Lower prevalence was found among urban residents (2%) and patients with gastrointestinal disorders (2%). There was only a slight difference in prevalence between individuals with co-infections (8%) and those without (7%). Studies using microscopy showed higher prevalence (7%) than molecular methods (4%). This is likely due to the misidentification of non-pathogenic Entamoeba species as E. histolytica when using microscopy. These findings contribute to a better understanding of the epidemiology of E. histolytica intestinal infection in Malaysia. Although the overall prevalence is relatively low, the results highlight the need for continued surveillance and more accurate diagnostic approaches to support targeted control.
Deaths from the accidental ingestion of poisonous Amanita mushrooms occur every year due to the lack of a specific antidote against α-amanitin poisoning. Intervention and treatment can be promptly carried out to avoid serious consequences when the toxin can be effectively detected in whole blood before liver toxicity develops. Aptamers are molecular recognition units similar to antibodies, capable of specifically recognizing and detecting small molecules such as α-amanitin for which monoclonal antibodies are difficult to prepare. However, α-amanitin has a small molecular size and limited binding sites, which bring difficulties to aptamer selection. Moreover, achieving highly specific detection of α-amanitin in whole blood remains challenging due to the presence of potentially interfering components, such as human serum albumin (HSA). For these problems, we propose an aptamer selection method for small-molecule target α-amanitin, combining target-immobilized and library-immobilized SELEX to select high-affinity aptamers. To exclude HSA interference, counter-selection was introduced to remove HSA-bound sequences. Through these strategies, we successfully selected a highly specific α-amanitin aptamer with nanomolar affinity.
Pyroptosis, a form of immunogenic cell death, can remodel the immunosuppressive tumor microenvironment; however, its clinical translation is challenged by difficulties in targeted induction and biosafety concerns. In this study we discovered that geldanamycin (GA) can interacts specifically with arginine 207 (R207) in caspase‑3, and efficiently cleaved caspase-3, significantly inducing high-efficiency pyroptosis. Although high-dose GA promoted pyroptosis and antitumor immunity, physiological toxicity and the induction of resistance mediated by immune checkpoints including PD-L1 and CD47 limited therapeutic efficacy. To address this, we developed biomimetic dual-targeting microparticles(MPs)functionalized with anti-PD-L1 and anti-SIRPα nanobodies. This strategy synergized targeted pyroptosis induction with dual immune checkpoint blockade, achieving complete tumor regression, reduced physiological toxicity, and induced a potent effector immune response in murine cancer models, presenting a promising combinatorial approach for lung cancer immunotherapy.
Genetic predisposition and alcohol consumption are risk factors for increased blood pressure (BP), but their interactions influencing BP remain understudied. We conducted population-specific and cross-population meta-analyses of genome-wide gene-alcohol (GxAlc) interactions affecting BP in >1.1M individuals from multiple populations. We identified 46 GxAlc interaction loci for BP, including 21 from one-degree-of-freedom interaction tests (PGxAlc<5×10-8; or <0.05/Meff, Meff independent BP associations at P<10-5), and 25 from two-degree-of-freedom tests of main and interaction effects (PGxAlc<0.05/M2df, M2df independent 2df-associations at P2df<5×10-8), including 7 novel and 39 known BP loci. The 12q24 locus highlights the genetic effect of BRAP-rs11066001 on BP, being ~6 times larger in current drinkers than in non-drinkers. Gene prioritization with 46 GxAlc loci identified 15 genes with ≥3 lines of evidence (location, literature, druggability, functional/regulatory annotation, or pathway analyses). Several loci showed sex- and population-specific effects and revealed biological pathways of alcohol's influence on BP, suggesting mechanisms underlying alcohol-induced hypertension.
Alternative splicing drives molecular diversity, yet livestock spliceopathies remain underrecognised despite their major economic impact. By synthesising evidence across major livestock species, we reveal how splicing defects disrupt production through recurrent patterns: splice variants in dosage-sensitive genes affect growth and fertility, breed-specific splice-regulatory changes drive disease susceptibility, and epigenetic modifications enable environmental adaptation. These patterns reflect evolutionary constraints and domestication pressures driving aberrant splicing in modern breeds. Recent technological advances enable systematic investigation and treatment: long-read sequencing uncovers hidden splicing complexity, while clustered regularly interspaced short palindromic repeats (CRISPR) and antisense oligonucleotides offer precision interventions. However, critical gaps persist in functional validation and population-scale mapping. Addressing these within the One Health framework will advance animal welfare, food security, and comparative medicine, positioning alternative splicing as a fundamental driver of phenotypic diversity.
Adults and pupae of black flies assigned to the Simulium (Simulium) multistriatum species-group collected from Sumatra, Indonesia in 1992 and 1994 were reexamined. As a result, three undescribed species were found besides S. (S.) fenestratum Edwards, the only species in this species-group so far described from Sumatra. These undescribed species are described as new: S. (S.) mutaralamense sp. nov., which is characterized in the female by the haired basal portion of the radial vein, in the male by the number of upper-eye (large) facets in 18 or 19 vertical columns and 19 or 20 horizontal rows and hind basitarsus entirely darkened, and in the pupa by the gill with eight filaments widely divergent when viewed laterally; S. (S.) lubuksulasihense sp. nov., which is similar to S. (S.) mutaralamense sp. nov., but differs by the male hind basitarsus yellow on its basal one-third; and S. (S.) liwaense sp. nov., which is characterized in the male by the smaller number of upper-eye (large) facets in 14 or 15 vertical columns and 16 horizontal rows, and in the pupa by the gill with eight filaments moderately divergent when viewed laterally, and all three anterodorsal trichomes unbranched on each side of the thorax. Taxonomic notes to distinguish these new species from their related species are given. The male and pupa of S. (S.) fenestratum are redescribed.